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Saturday, January 30, 2016

Vascular protection by tetrahydrobiopterin: progress and therapeutic prospects


Tetrahydrobiopterin (BH4) is an essential cofactor required for the activity of endothelial nitric oxide (NO) synthase. Suboptimal concentrations of BH4 in the endothelium reduce the biosynthesis of NO, thus contributing to the pathogenesis of vascular endothelial dysfunction. Supplementation with exogenous BH4 or therapeutic approaches that increase endogenous amounts of BH4 can reduce or reverse endothelial dysfunction by restoring production of NO. Improvements in formulations of BH4 for oral delivery have stimulated clinical trials that test the efficacy of BH4 in the treatment of systemic hypertension, peripheral arterial disease, coronary artery disease, pulmonary arterial hypertension, and sickle cell disease. This review discusses ongoing progress in the translation of knowledge, accumulated in preclinical studies, into the clinical application of BH4 in the treatment of vascular diseases. This review also addresses the emerging roles of BH4 in the regulation of endothelial function and their therapeutic implications.

http://www.sciencedirect.com/science/article/pii/S0165614708002435

http://www.nature.com/npp/journal/v37/n1/full/npp2011205a.html

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